ArticleACS infectious diseases2016
Plasmodium falciparum Cyclic Amine Resistance Locus (PfCARL), a Resistance Mechanism for Two Distinct Compound Classes.
Article in ACS infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
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- Chemoprevention of malaria with long-acting oral and injectable drugs: an updated target product profile.Malaria journal · 2024Review
- Plasmodium SEY1 is a novel druggable target that contributes to imidazolopiperazine mechanism of action.Research square · 2024Article
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- Antimalarial drug discovery: progress and approaches.Nature reviews. Drug discovery · 2023Review
- Potent acyl-CoA synthetase 10 inhibitors kill Plasmodium falciparum by disrupting triglyceride formation.Nature communications · 2023Article
- Fast-Killing Tyrosine Amide ((ACS infectious diseases · 2023Article
- Promising antimalarial hits from phenotypic screens: a review of recently-described multi-stage actives and their modes of action.Frontiers in cellular and infection microbiology · 2023Review
- Current and emerging target identification methods for novel antimalarials.International journal for parasitology. Drugs and drug resistance · 2022Review
- AssessmentAntimicrobial agents and chemotherapy · 2022Article
- Assessing risks of Plasmodium falciparum resistance to select next-generation antimalarials.Trends in parasitology · 2021Review
- MalDA, Accelerating Malaria Drug Discovery.Trends in parasitology · 2021Review
- Absence of Association between Methylene Blue Reduced Susceptibility and Polymorphisms in 12 Genes Involved in Antimalarial Drug Resistance in AfricanPharmaceuticals (Basel, Switzerland) · 2021Article
- The antimalarial efficacy and mechanism of resistance of the novel chemotype DDD01034957.Scientific reports · 2021Article
- Efforts Made to Eliminate Drug-Resistant Malaria and Its Challenges.BioMed research international · 2021Review
- Lerisetron Analogues with Antimalarial Properties: Synthesis, Structure-Activity Relationship Studies, and Biological Assessment.ACS omega · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
MMV007564 is a novel antimalarial benzimidazolyl piperidine chemotype identified in cellular screens. To identify the genetic determinant of MMV007564 resistance, parasites were cultured in the presence of the compound to generate resistant lines. Whole genome sequencing revealed distinct mutations in the gene named Plasmodium falciparum cyclic amine resistance locus (pfcarl), encoding a conserved protein of unknown function. Mutations in pfcarl are strongly associated with resistance to a structurally unrelated class of compounds, the imidazolopiperazines, including KAF156, currently in clinical trials. Our data demonstrate that pfcarl mutations confer resistance to two distinct compound classes, benzimidazolyl piperidines and imidazolopiperazines. However, MMV007564 and the imidazolopiperazines, KAF156 and GNF179, have different timings of action in the asexual blood stage and different potencies against the liver and sexual blood stages. These data suggest that pfcarl is a multidrug-resistance gene rather than a common target for benzimidazolyl piperidines and imidazolopiperazines.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.